Alcoholism may affect on the order of 20% of men and 5% of women in the United States. Recent data indicates a heterogenous genetic component for alcoholism and investigation of young men from alcoholic families, known to be at high risk (HR) for alcoholism, has revealed that they demonstrate an attenuated response to the impairing effects of ethanol compared to young men without a family history of alcoholism (LR). This difference is not due to different ethanol levels. The present proposal is designed to investigate whether the neuropeptide, thyrotropin-releasing hormone (TRH), known through animal studies to counteract ethanol's depressant effects, modifies the behavioral effects of ethanol in humans. To test for an effect of TRH on ethanol-induced behavior, eight male LR subjects, ages 21-25, will be selected. A battery of neuropsychological tests, e.g., choice reaction time, free recall, chosen for their sensitivity to ethanol will be given to all subjects during a double-blind, randomized, balanced challenge study using four conditions: placebo- placebo, placebo-TRH (2,000 ug), ethanol 0.8 gm/kg-placebo, ethanol 0.8 gm/kg-TRH (2,000 ug). The effect of ethanol on memory, disinhibition, reaction time, motor performance, and subjective state will be compared to placebo and to TRH-ethanol. If TRH modulates one or more of the behavioral effects of ethanol this would have implications for understanding the neurobiology of ethanol in humans and could be important for understanding the different responses to ethanol observed in HR compared to LR subjects.